Ajulemic acid

Ajulemic acid (CT3, 8.9) is the dimethylheptyl homolog of the main metabo-hte of A8-THC. It has no psychotropic activity, but has analgesic and antiinflammatory effects. 

The dimethylheptyl side-chain analogue of 9-carboxy-A -THC, ajulemic acid, CT-3, (166) is currently in clinical development for treatment of pain and inflammation [121, 122]. Compound (166) does show some affinity for CBi and CB2 receptors, but may also exert anti-inflammatory and analgesic effects through other mechanisms. It does not appear to be psychoactive in humans [123]. 

Ajulemic acid (77) Cannabinoid CP 7075 (IP 751, ajulemic acid, CT-3) (synthetic version) Neurological (neuropathic pain) Suppresses IL-lp and mahix metalloproteinases (MMPs) through a peroxisome proliferator-activated receptor (PPAR) y-mediated mechanism Phase I Cervelo Pharmaceuticals 615-618... 

Burstein SH, Karst M, Schneider U, Zurier RB. (2004) Ajulemic acid A novel cannabinoid produces analgesia without a high . Life Sci 75 1513-1522. 

Recent work has aimed at developing cannabinoids that lack psychotropic side effects, which limit dosing. One example of this may be found in fhe THC and cannabidiol acid derivatives ajulemic acid (CT-3) and HU-320. These compounds were reported to produce anti-inflammatory effects with a reduced side effect profile (Burstein et al. 1998 Burstein et al. 2004 Sumariwalla et al. 2004), perhaps because they possess either poor (ajulemic acid) or virtually no (HU-320) affinity for either CBIR or CB2R. Consequently, the mechanism by which they produce analgesic effects is not clear. In a recent clinical trial of patients suffering from neuropathic pain, ajulemic acid possessed some efficacy (Karst et al. 2003). While many questions about these and similar compounds are awaiting further research, this appears to be an important line of inquiry. 

Since non-psychoactive cannabinoids, such as CBD and CBN, are able to induce a marked decrease in the levels of interferons, pro-inflammatory cytokines, and chemokines after stimulation with LPS [63], this activity is unlikely to be mediated by interaction with CB receptors, while the involvement of the adenosine signaling has, rather, been postulated [64], CBD and CBG have also demonstrated a non-CB-mediated inhibition of the proliferation of human keratinocytes, supporting a potential role for cannabinoids in the treatment of psoriasis [65]. A synthetic cannabinoid, ajulemic acid (31), has been proposed for treatment of arthritis and for the management of pain and inflammation in multiple sclerosis patients [66]. 

Ajulemic acid, aliskiren, amantadine, azacitidine, carbovir, carvedilol, dextran, diclofenac, isosorbide, lamivudine, 2 -fluoro-5-methyl-beta-L-arabinofuranosyl uracil, flunixin, fulvestrant, gefitinib, ibuprofen, imatinib, indomethacin, ketoprofen, lumiracoxib, madol, mefenamic acid, metronidazole, midazolam, naproxen, oritavancin, oxyphenbutazone, phenazopyridine, phenylbutazone, piroxicam, pravastatin, salicylic acid, spiramycin, synthetic insulins, tenofovir, tolmetin, trimetazidine vitamins B5,... 

A GC-MS method combined with solid-phase extraction to detect ajulemic acid (AJA), a nonpsychoactive synthetic cannabinoid in human plasma. The calibration cnrve exhibits two linear portions between 10 and 750 ng/ml, and 750 and 3000 ng/ml, respectively. Intra- and interday precision values (expressed as the percentage of the RSD value) for the two segments of the calibration curves 1.5-7.0 and 3.6-7.9, respectively. Detection limit 10 ng/ml. The amount of the glucoronide derivative could be estimated by comparing the free AJA levels with those obtained after enzymatic hydrolysis. The method was tested on 21 patients suffering from neuropathic pain with hyperalgesia and allodynia. 

Batista, C., Berisha, M., Karsf M., Salim, K., Schneider, U. and Brenneisen, R., Determination of ajulemic acid and its glucuronide in human plasma by gas chromatography-mass spectrometry. J. Chrorruitogr. B, 820(1), 77-82 (2005). 

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